Hybrid New Zealand Black/New Zealand White (NZB/NZW) mice are animal models of systemic lupus erythematosus (SLE). The immunosuppressive drug cyclophosphamide is currently used to treat selected patients with SLE and other inflammatory diseases of connective tissue. Prolonged therapy with immunosuppressive drugs may suppress immune surveillance mechanisms and increase the risk of developing neoplastic disease. Earlier work in this laboratory showed that 94% of NZB/NZW mice receiving prolonged therapy with cyclophosphamide developed tumors. Untreated animals had a tumor incidence of 9%. Further studies have confirmed the augmented incidence of neoplasms in hybrid New Zealand mice receiving cyclophosphamide administered according to 3 additional treatment protocols. Tumors also appeared in NZB/NZW mice treated with hydrocortisone. This information suggests that manipulation of the abnormal immune systems of these animals with several immunosuppressive drugs may increase the occurrence of tumors. Ongoing projects in this laboratory include therapy with an interferon-inducing agent, transplantation studies, and identification of paraproteins in sera of lymphoma-bearing mice.